Application of american ginseng to enhance neurocognitive function

ABSTRACT

Disclosed are methods of enhancing neurocognitive function by administering of American Ginseng. Preferred dosages in the range of 5 to 50 mg total genosides enhance cognitive function—including, improvement of working memory (WM) performance, attentional performance (e.g., Choice Reaction Time accuracy), and calmness.

FIELD OF THE INVENTION

The present invention relates to the use of American Ginseng (Panaxquinquefolius) to increase neurocognitive function (for example, memory,attention, and calmness, among others).

BACKGROUND OF THE INVENTION

The term “Ginseng” is generally used to refer to the species of thegenus Panax of the family Araliaceae. Extracts of Asian Ginseng (Panaxginseng) have been used for millennia in Traditional Chinese Medicinefor the prevention and treatment of a variety of diseases, and have beenalso used as general health elixirs and performance enhancers (includingin the neurocognitive area). There is a growing body of evidence tosupport Asian Ginseng as a cognitive enhancer. American Ginseng (Panaxquinquefolius) is also in the family Araliaceae, although until now thecognition-enhancing properties of American Ginseng have not been known.

Research evaluating behavioural effects of chronic administration ofAsian Ginseng in animals has demonstrated attenuation of learningdeficits in aged rodents (Wen, T. C. et al. (1996) “Ginseng rootprevents learning disability and neuronal loss in gerbils with 5-minuteforebrain ischemia,” Acta Neuropathol 91:15-22; Zhao, R. & McDaniel, K.(1998) “Ginseng improves strategic learning by normal and brain-damagedrats,” NeuroReport 9:1619-1624; Nitta, H. et al. (1995) “Panax Ginsengextract improves the scopolamine-induced disruption of 8-arm radial mazeperformance in rats” Biol Pharm Bull 18:1439-1442). In one study, notonly was learning improved in gerbils with learning deficits associatedwith forebrain ischemia, but Asian Ginseng was also neuroprotective,rescuing hippocampal CA1 pyramidal neurons (Wen et al. 1996). In youngrodents, Asian Ginseng-related improvements may follow an invertedU-dose response. Mice administered 3, 10, 30, 100 & 300 mg/kg Asian(extract G115) improved performance following 10 mg/kg in aninverted-U-dose-response manner. However this effect was observed for aselection of tasks only (Petkov, V. D. & Mosharrof, A. H. (1987)“Effects of standardized Ginseng extract on learning, memory andphysical capabilities,” Am J Chin Med 15:19-29). Studies have observedcognitive benefits over a range of dosages of Asian Ginseng, rangingfrom 10 mg/kg to 150 mg/kg (Petkov & Mosharrof, 1987; Petkov V. D. etal. (1993) “Memory effects of standardized extracts of Panax Ginseng(G115), Ginkgo biloba (GK 501) and their combination Gincosan(PHL-00701),” Planta Med 59:106-114), with some doses appearing toimpair cognitive function. For example, Petkov & Mosharrof (1987) foundthat higher dosages of Asian Ginseng G115 (300 mg/kg) impairedconditioned reflex activity in rats. The dose-response profile of AsianGinseng is further complicated by variations in methods of assessment,age and dosage (Petkov et al. 1993)

In the few chronic administration studies on human subjects beneficialeffects of Asian Ginseng were observed in cognitive deficit populations.For example, Neri et al. administered an Asian Ginseng-containingvitamin complex or placebo for 9 months and examined performance ofparticipants suffering from age-related cognitive decline (Neri, M. etal. (1995) “Influence of a double blind pharmacological trial on twodomains of well being in subjects with age associated memoryimpairment,” Arch Gerontol Geriatr 21:241-252). They observedimprovement of mnemonic performance following Asian Ginseng. Innon-insulin dependent diabetic patients 8-week administration of 200 mgAsian Ginseng improved psychophysical performance compared to placebo(Sotaniemi, E. A. et al. (1995) “Ginseng therapy innon-insulin-dependent diabetic patients,” Diabetes Care 18:1373-1375).One study aimed to assess the effects of an Asian Ginseng supplementcombination ‘Gericomplex’ (Asian Ginseng, vitamins, minerals and traceelements) on mental health and wellbeing of geriatric patients. Twocapsules were taken daily for 8 weeks, but they failed to observe anycognitive enhancement by the intervention (Thommessen, B. & Laake, K.(1996) “No identifiable effect of Ginseng (Gericomplex) as an adjuvantin the treatment of geriatric patients,” Aging 8:417-420). In healthyindividuals over the age of 40 Sorensen & Sonne administered 400 mg ofstandardized Asian Ginseng extract for 8 to 9 weeks and observedsignificantly faster reaction times compared to placebo (Sorensen, H. &Sonne, J. (1996) “A double masked study of the effects of Ginseng oncognitive functions,” Curr Ther Res 57:959-968). In healthy youngindividuals D'Angelo et al. found that following 12 weeks of treatmentof either 100 mg of Asian Ginseng (G115) or placebo (taken twice daily),patients administered Asian Ginseng demonstrated mental arithmetic(D'Angelo, L. et al. (1986) “A double-blind, placebo-controlled clinicalstudy on the effect of a standardized Ginseng extract on psychomotorperformance in healthy volunteers,” J Ethnopharmacol 16:15-22). Howeverthese data should be interpreted with caution as the above studies havebeen criticized on a number of methodological issues such as inadequatesample sizes, non-standardised treatments, and inadequate researchdesigns and statistical analysis (see Bahrke, M. S. & Morgan, W. P.(1994) “Evaluation of the ergogenic properties of Ginseng,” Sports Med18:229-248; Bahrke, M. S. & Morgan, W. P. (2000) “Evaluation of theergogenic properties of Ginseng: an update,” Sports Med 298:113-133;Kennedy, D. O. et al. (2003) “Modulation of mood and cognitiveperformance following administration of single doses of Melissaofficinalis (Lemon balm) with human CNS nicotinic and muscarinicreceptor binding properties,” Neuropsychopharmacology 28: 1871-1881).

In a series of studies assessing the effects of acute administration ofAsian Ginseng on cognition in young healthy individuals, enhancement byAsian Ginseng was observed largely for ‘secondary memory’ (a compositeof four secondary memory tasks). (Kennedy et al. 2003; Scholey, A. B. &Kennedy, D. O. (2002) “Acute, dose-dependent cognitive effects of Ginkgobiloba, Panax ginseng and their combination in healthy young volunteers:differential interactions with cognitive demand,” Hum Psychparmacol Clin17:35-44). In the first study, doses of 200, 400 and 600 mg AsianGinseng (G115) were administered (Kennedy, D. O., et al. (2001a)“Differential, dose-dependent changes in cognitive performance and moodfollowing acute administration of Ginseng to healthy young volunteers.”Nutr Neurosci 4:295-310). Enhancement of ‘secondary memory’ was foundfollowing 400 mg at four post-dose testing sessions, while the lower andhigher dosage diminished performance for ‘speed of attention’ (Id.)

In a further study, assessing combinations of Asian Ginseng and Ginkgo(ratio 100:60) at dosages of 320, 640, 960 mg, a similar pattern wasobserved (Kennedy, D. O. et al. (2001b) “Differential, dose dependentchanges in cognitive performance following acute administration of aGinkgo biloba/Panax Ginseng combination to healthy young volunteers,”Nutr Neurosci 4:399-412). With performance of secondary memory beingimproved by 960 mg, and reduced performance on speed of attention forthe other dosages (320 and 640 mg) (Id.). A later study, replicated thefinding that a 400 mg dosage improves “secondary memory.” Further studyalso assessed the effect of 200, 400 and 600 mg Asian Ginseng on mentalarithmetic performance, where cognitive demand was manipulated (Kennedy,D. O., et al. (2002a) “Modulation of cognition and mood followingadministration of single doses of Ginkgo biloba, Ginseng and aGinkgo/Ginseng combination to healthy young adults,” Physiol Behav72:953-964). Again this task was improved by a 400 mg dosage but onlyfor the most demanding version of the task (Serial Sevens) (Reay, J. L.et al. (2005) “Single doses of Panax ginseng (G115) reduce blood glucoselevels and improve cognitive performance during sustained mentalactivity,” J Psychopharmacol. 19(4):357-65; Reay, J. L. et al. (2006)“Effects of Panax ginseng, consumed with and without glucose, on bloodglucose levels and cognitive performance during sustained ‘mentallydemanding’ tasks,” J Psychopharmacol 20(6):771-81.) It appears to be thecase that Asian Ginseng or its constituents are capable of producingtangible cognitive enhancing effects and that for Asian Ginseng 200 or400 mg appears to be an optimal dose for young healthy adults whenadministered acutely prior to a cognitive test.

The constituents of Asian Ginseng (Panax ginseng) that are thought tocontribute to its bioactivity are the ginsenoside saponins. Ginsenosidescan be classified into three groups on the basis of their chemicalstructure; the Panaxadiol group (Rb1, Rb2, Rb3, Rc etc.), Panaxatriolgroup (Re, Rf, Rg1, Rg2, Rh1), and the oleanolic acid group (e.g. Ro).

American Ginseng (Panax quinquefolius), by contrast, has its owncharacteristic profile exhibiting a high expression of the GinsenosideRb1. The American Ginseng extract used in the present study contains11.65% Ginsenosides (Rb1 (5.68%), Re (2.05%), Rc (1.86%), Rd (1.47%),Rb2 (0.029%), Rg1 (0.027%)).

Many of these ginsenosides have been isolated and evaluated forpharmacological effects in animal and human models. They have beenreported to exert effects on the cholinergic system; isolated Rb1 wasboth observed to increase synaptosomal choline uptake, and stimulateacetylcholine release (Benishin, C. G. et al. (1991) “Effects ofginsenoside Rbl on central cholinergic metabolism,” Phlrmanacology42:223-229; Benishin, C. G. (1992) “Actions of ginsenoside Rbl oncholine uptake in central cholinergic nerve endings,” Nelnrochenm21:1-5). Ginsenosides Rg1 and Rb1 have also been found to elicit markedalterations in brain serotonin concentrations (Zhang, J. T. et al.(1990) “Preliminary study on antiamnestic mechanism of ginsenoside Rgland Rbl,” Chin Med J 103:932-938). Furthermore Salim found that in ratbrains Rb1 increased expression of choline acetyltransferase and nervegrowth factor messenger RNA (Salim, K. N. et al. (2004) “Ginsenoside Rblregulates ChAT, NGF and trkA mRNA expression in rat brain,” Braini ResMol Brait Res 1997 47:177-182). Other ginsenosides have also beenreported to effect specific physiological mechanisms, ginsenoside Rd hasbeen reported to affect corticosterone secretion (Hiai, S. et al. (1983)“Evaluation of corticosterone secretion-inducing activities ofginsenosides and their prosapogenins and sapogenins,” Cltern PharmiiBlill (Tokyo) 1:168-174) and ginsenosides Rd and Re may inhibitsynaptosomal uptake of norepinephrine, dopamine, serotonin and GABA(Tsang, D. et al., (1985) “Ginseng saponins: influence onneurotransmitter uptake in rat brain synaptosomes,” Planta Med47:221-224). Furthermore in vivo modulation of LTP in the hippocampalformation by Ginsenoside Rb1 has been observed in rats (Abe, K. et al.(1994) “Differential effects of ginsenoside Rb1 and malonylginsenosideRb1 on long-term potentiation in the dentate gyrus of rats,” Brain Res.649(1-2):7-11.)

With respect to evaluating potential cognitive enhancement by wholeextract American Ginseng (Panax quinquefolius), one study observed thatscopolamine induced amnesia in Sprague-Dawley rats was attenuated byadministration of American Ginseng. American Ginseng attenuated thescopolamine-associated decrement on performance of the Morris water mazetask (spatial learning) and increased choline uptake in synaptosomalpreparations (Sloley, B. D., et al. (1999) “American Ginseng extractreduces scopolamine induced amnesia in a spatial learning task,” JPsychiatry Neurosci 24:442-452). However, studies assessing thepsychogenic benefits of American Ginseng are rare.

SUMMARY OF THE INVENTION

Until now, the beneficial effects of American Ginseng on cognitivefunction have not been known. The present invention provides methods ofusing American Ginseng to enhance cognitive function—including,improvement of working memory, attention, and calmness, among others.The inventors have discovered that administering American Ginsengimproves working memory (WM) performance: spatial span was improved byall doses at all testing times; other WM tasks were differentiallyimproved by the 200 mg dose (with time- and task-specific benefitsassociated with other doses). Also, attentional performance (ChoiceReaction Time accuracy) was significantly improved by 100 mg at alltimes and by 200 and 400 mg after 6 h. Furthermore, the 100 mg dose wasassociated with significantly enhanced “calmness” at 3 h and 6 h.

BRIEF DESCRIPTION OF THE DRAWINGS

Further features, advantages and characteristics of the presentinvention will become apparent to a person of ordinary skill in the artin view of the following detailed discussion of preferred embodiments ofthe present invention, made with reference to the drawings annexed, inwhich:

FIG. 1 illustrates: (A) Chromatogram of the American ginseng (Panaxquinquefolius) extract; and (B) Structures of ginsenosides; and

FIG. 2 illustrates the significant effects of Panax quinquefolius oncognitive function and mood. Graphs depict mean change-from-baselinescores following a placebo and 100 mg, 200 mg and 400 mg of astandardised extract. Significant differences from placebo at each timepoint are indicated (*, p<0.05)

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to the novel discovery that acuteconsumption of Panax quinquefolius (American Ginseng) can improvecognitive performance and increase calmness in healthy young adults. Alldoses of Panax quinquefolius were found to improve some aspect ofcognition.

In addition to being administered whole, American Ginseng can beadministered as an extract, powder, or in other modified form. Based onthe modifications, the amount of ginsenosides present may vary. Forexample, Naturex produces milled root form of American Ginseng(PurePowder), which contain total ginsenosides content between about 3and 7% (usually standardized to 5%). Naturex also produces an extract ofAmerican Ginseng, which contain total ginsenosides content betweenamount 7 to 16% (usually standardized to 10%). The distribution ofginsenosides is similar in all products and a person of ordinary skillin the art would understand how to make other powders, extracts, andmodified products containing ginsenosides. The composition describedbelow in connection with a preferred embodiment of the present inventionis an extract of American Ginseng containing 11.65% of totalginsenosides.

American Ginseng can be administered in a range of doses, which canbenefit different domains of cognitive function. All doses appeared havesome cognitive effects with optimal doses appearing to have sometask-specificity. Perhaps the most striking and surprising result wasthat all three doses improved Corsi block performance compared toplacebo at all post-dose time points with the most beneficial effectsbeing observed for the lower two doses. A preferred embodiment of thepresent invention involves improving Immediate Word Recall accuracy andNumeric Working Memory speed by administering a 200 mg dose. Anotherpreferred embodiment involves improving Alphabetic Working Memory speedby administering 100 mg or 400 mg doses. Another preferred embodimentinvolves improving Choice Reaction Time accuracy by administering a 100mg or 400 mg dose 1 hour in advance of desired results. A furtherpreferred embodiment for improving Choice Reaction Time involvesadministering 100 mg at least 3 hours before desired results, andfurther preferred to be administered 6 hours before desired results.

For improving Immediate Word Recall and Numeric Working Memory,preferred embodiments involve a dose of 200 mg. For other tasks (ChoiceReaction Time, Alphabetic Working Memory and the Corsi block task) bothhigh and low dosages appeared to improve performance. It is furtherpreferred that the American Ginseng be administered 6 hours in advanceof desired results. As used herein, the term “high dose” refers to adosage of between 400 and 500 mg, and the term “low dose” refers to adosage of between 50 and 400 mg.

American Ginseng also has beneficial effects on mood in healthy youngadults. For example, 100 mg of Panax quinquefolius improves feelings ofcalmness in a time dependent manner. This effect was significantlyhigher 3 h and 6 h following administration compared to placebo. Incontrast, a number of studies have assessed the effect of Asian Ginseng(Panax ginseng) on mood using the Bond Lader mood scale (Kennedy et al.2001a; Kennedy et al. 2001b; Kennedy et al. 2002a; Kennedy et al. 2003;Scholey & Kennedy 2002), the same scale used in connection with thepresent invention. These studies all assessed the acute effects of AsianGinseng on mood. One study demonstrated an effect of Asian Ginseng onmood in that at 200 and 400 mg dosages feelings of alertness declined6-hours following treatment of Asian Ginseng (Kennedy et al. 2001a).

Another study assessed the effects of acute administration of AsianGinseng on fatigue in healthy young individuals (Reay et al., 2005) andobserved that subjective feelings of mental fatigue were ameliorated ina time-dependent manner by 200 mg Ginseng during sustained intensecognitive processing. (The present invention found that self-ratedcalmness was reduced over the course of testing following placebo and100 mg American Ginseng extract essentially produced increased feelingof calmness, possibly tapping into feelings of fatigue which increasedwith cognitive testing and were stabilized by 100 mg treatment.) It maybe that effects were most pronounced at the later time point due toincreasing stress levels over the testing phase, in which case we mightattribute an adaptogenic effect might be attributed to the ginsengextract. Previous research in rodents has shown that Ginseng saponinsand Ginsenoside Rb1 inhibit the stress-induced increases in plasmacorticosterone (Kim, H. S. et al. (1998) “Effects of ginsenosides onCa2+ channels and membrane capacitance in rat adrenal chromaffin cells,”Brain Res Bull. 46(3):245-51.)

The present invention relates to the enhancement effects of AmericanGinseng (Panax quinquefolius) predominantly on working memory (WM)processes (Corsi block, and both Numeric and Alphabetic Working Memory).This also related to positive effects on short-term verbal declarativememory (Immediate Word Recall) and attention (Choice Reaction Time). WMand short-term memory systems are thought be localized to hippocampaland pre-frontal cortices. It is generally agreed that the hippocampushas an important role in the formation of new memories about experiencedevents such as episodic or autobiographical memory. While the prefrontalcortex deals with higher-order working memory/executive functionsincluding manipulating working memory (Gabrieli, J. D. (1998) “The roleof left prefrontal cortex in language and memory,” Proc Natl Acad SciUSA 95:906-913; Goldman-Rakic, P. S. (1996) “The prefrontal landscape:Implications of functional architecture for understanding humanmentation and the central executive [and discussion],” PhilosophicalTransactions of the Royal Society of London, Series B: BiologicalSciences 351:1443-1453), it has been well documented that thecholinergic pathways projecting to the cerebral cortex and hippocampusplay a key role in learning and memory and it has been argued that thebrain cholinergic system is a specific target for cognitively enhancingagents (Giovannini, M. G. et al. (1995) “Differential regulation byN-methyl-D-aspartate and non-N-methyl-D-aspartate receptors ofacetylcholine release from the rat striatum in vivo,” Neuroscience65(2):409-15.) A number of studies have identified cholinergicproperties associated with isolated ginsenosides. A direct interactionbetween Rg2 and nicotinic receptor subtypes has been observed (Sala, F.et al. (2002) “Effects of ginsenoside Rg2 on human neuronal nicotinicacetylcholine receptors,” J Pharmacol Exp Ther. 301(3):1052-59.)Moreover Benishin (1992) demonstrated modulation by Rb1 of acetylcholinerelease and reuptake, along with a number of choline uptake sites in thehippocampus, and to a lesser extent, the cortex. Both ginsenosides Rg1(Zhang et al. 1990) and Rb1 (Salim et al. 2004; Zhang et al. 1990) havealso been shown to increase choline acetyltransferase levels in rodentbrains.

In animal research, one study observed that scopolamine-induced deficitsare attenuated by American Ginseng (Panax quinquefolius) in SpragueDawley rats (Sloley et al. 1999). Protection against scopolamine-inducedamnesia by American Ginseng was most evident in trials where animalswere required to remember the task learned the previous day. In thisstudy it was also observed that American Ginseng increased cholineuptake into synaptosomes prepared from rat brain. Also, in the humanbrain crude extracts of Asian Ginseng exhibited an affinity for bothnicotinic and muscarinic receptors in cerebral cortex membranes, (Lewis,R. et al., “Non-ginsenoside nicotinic activity in ginseng species,”Phytother Res. 13(1):59-64.)

As discussed previously, the American Ginseng extract profile has 2-3times the ginsenoside content than the more commonly researched AsianGinseng, with the highest expression of Rb1 and Re. The cholinergicsystem is one potential central mechanism of action on the enhancementof memory by American Ginseng.

The inventors also assessed the acute effects of American Ginseng (Panaxquinquefolius) on glucoregulation on young healthy adults. Vuksan et al(2000) previously observed that 300 mg Panax quinquefolius lowered bloodglucose levels during a glucose challenge in both healthy and diabeticsubjects. (Vuksan, V. et al. (2000a) “American ginseng (Panaxquinquefolius L) reduces postprandial glycemia in nondiabetic subjectsand subjects with type 2 diabetes mellitus,” Arch Intern Med.160(7):1009-13.) Other studies also observed similar results: AmericanGinseng appeared to have significant hypoglycaemic action in rodents(Oshima, Y. et al. (1987) “Isolation and hypoglycaemic activity ofquinquefolans A, B, and C, glycans of Panax quinquefolium roots,” J NatProd 50:188-190; Martinez, B. & Staba, E. J. (1984) “The physiologicaleffects of Aralia, Panax and Eleutherococcus on exercised rats,” Jpn JPharmacol 35:79-85). In humans, American Ginseng also reduced bloodglucose levels following a 25-g glucose challenge in both diabeticpatients who had ingested 300, 600, and 900 mg and non diabeticsadministered 100, 200, and 300 mg (Vuksan, V. et al., 2000a; Vuksan, V.et al. (2000b) “Similar postprandial glycemic reductions with escalationof dose and administration time of American Ginseng in type 2 diabetes,”Diabetes Care 23:1221-1226; Vuksan, V. (2006) “Korean red Ginseng (PanaxGinseng) improves glucose and insulin regulation in well controlled type2 diabetes: results of a randomized, double-blind, placebo-controlledstudy of efficacy and safety,” Nutr Metab Cardiovasc Dis 18:46-56)(Vuksan et al. 2000a). The present invention, however, shows that, atleast at the dosages used here (100 mg, 200 mg, and 400 mg), AmericanGinseng has no detectable effect on blood glucose levels.

Overall the present invention is the first to demonstrate cognitive andmood enhancement following Panax quinquefolius administration.Cognition-enhancing effects of the present invention were observedacross a range of cognitive modalities at a range of dosages. The lackof glycaemic effects also highlights important methodologicaldifferences between existing literature and the present invention, andthus one of ordinary skill in the art will more fully understand howAmerican Ginseng's impact on glucose levels may be moderated.

EXAMPLES

The results of each of the following examples were tested by arandomized, double-blind, placebo-controlled, cross-over trial (N=32healthy young adults) to evaluate the acute mood, neurocognitive andblood glucose effects of 3 doses (100, 200, 400 mg) of an Americanginseng extract (standardized to 10.65% ginsenosides) compared toplacebo. On study days (separated by a >7-day wash-out) participantsunderwent a baseline assessment of mood, cognitive function and bloodglucose. They then took the day's treatment followed by the sameassessments 1, 3 and 6 hours later. Statistical analysis used a two-way(Treatment×Time) ANOVA followed by pre-planned comparisons of eachdose's effects compared with placebo at each time point.

Participants

Thirty two participants (16 male, 16 female) were recruited viaadvertisements in local newspapers and university bulletin boards totake part in the study. Ages ranged from 18 to 40 years (M=25.2,SD=4.97). All participants reported that they were in good health, nottaking any drugs or medications (excluding the contraceptive pill), hadno known food allergies and were non smokers.

They completed an initial health screening questionnaire which excludedparticipants with a number of medical conditions (e.g. diabetes,hypoglycaemia, psychiatric disorders, epilepsy, and gastrointestinaldisorders) or who were on prescribed medications, were pregnant orlactating. They were advised to refrain from taking any vitamins, otherherbal supplements and over the counter medicines for the whole periodof study. On the testing days, participants were advised to abstain fromconsuming alcohol, caffeine products and energy drinks. They wererequired to eat a light breakfast (toast or cereal) at least 2 hoursbefore the onset of the experiment and were provided with sandwich forlunch (with either chicken and salad, or cheese and salad). The studywas approved by the Swinburne University Human Research Ethics Committeeand all participants gave written informed consent. The study wasconducted according to the Declaration of Helsinki. Volunteers receiveda 200 AUD cheque at the end of the study for their participation.

Treatments

The coated capsules utilized in the study contained a standardized to10% Ginsenosides commercial extract of Panax quinquefolius (AmericanGinseng) prepared and provided by Naturex.

Extract Preparation

The roots of American ginseng (Panax quinquefolius) were authenticatedusing macroscopic, microscopic, and high performance thin layerchromatography techniques (Reich, E. & Schibli (2007) “A In:High-Performance Thin-Layer Chromatography for the Analysis of MedicinalPlants,” ISBN: 9781588904096, Thieme Medical Publishers Inc., New York,N.Y.). The American ginseng extract was obtained through an industrialprocess (Naturex, USA, Reference: 331350, Lot number: E15/05/D8). First,the ginseng roots were ground to be between ¼ and ½ inch, and then theground roots were soaked three times during five hour intervals in anethanol/water (75/25, v/v) solution at 40° C. After filtration, theclarified solution was then concentrated under vacuum at 45° C. Thethree pools were combined and concentrated again until the total solidson dry basis were around 60%. This is the Native Extract, which was thenmixed with maltodextrine as a carrier and spray dried to obtain a finepowder. The moisture content in the extract was less than 5%. Afterextraction, the sample was analyzed for its content of pesticides (USP.General Chapters: <561> Articles of Botanical Origin. Test forPesticides. USP-31-NF26 S1, Rockville, Md. 2008) and heavy metals(method 993.14, AOAC, Official Methods of Analysis (2005) 18th Ed. AOACInternational, Gaithersburg, Md.) at Covance Laboratories (Madison,Wis., USA) for compliance. The American ginseng extract was found to bebelow the Maximum Residue Limits established for pesticides and heavymetals (Durgnat, J. M. et al. (2005) “Quality and safety assessment ofginseng extracts by determination of the contents of pesticides andmetals,” Food Additives & Contaminants 22:1224-1230).

The American ginseng extract used in this clinical trial contained 0.28%of Rg₁, 2.06% of Re, 5.69% of Rb₁, 1.87% of Rc, 0.29% of Rb₂, and 1.48%of Rd. The total ginsenosides, calculated as the sum of above individualginsenosides, represented 11.65% in the American ginseng extract. Asexpected, the ginsenoside Rf was not found (Harkey, M. R. et al. (2001)“Variability in commercial ginseng products: an analysis of 25preparations,” Am J Clin Nut 73:1101-1106). The ginsenoside Rf is notpresent in American ginseng but it is present in Asian ginseng (Panaxginseng), and is used as a marker to determine adulterations in Americanginseng. The chromatogram of the American ginseng extract and thestructures of its ginsenosides is presented in FIG. 1.

Initial one-way analyses on each cognitive and mood measure revealed nosignificant baseline differences between conditions confirming thatpost-treatment effects were not attributable to change differences inbaseline performance. Significant effects associated with treatments arepresented in FIG. 2.

Example 1

Administering American Ginseng served to improve Choice Reaction Time inthe following situation.

Choice Reaction Time: The arrow pointing to the left or right waspresented in the centre of the screen at irregular time intervals. Thevolunteer makes a response with ‘left’ and ‘right’ cursor buttons toarrows pointing to the left or right respectively as quickly aspossible. Each of the 15 stimuli remained on screen until the key presswas registered. The inter-stimulus interval randomly varying between 1and 3 seconds. Outcomes were accuracy (% correct) and reaction time(ms).

Four Choice Reaction Time: A replica of the four direction arrow keysfound at the bottom and to the right of the computer keyboard appearedon the screen. The participants were instructed to make a response asquickly and as accurately as possible with ‘left’, ‘right’, ‘up’ and‘down’ cursor keys corresponding to the arrow being illuminated on thescreen one at a time, pointing randomly to the left, right, up or down.Each of the 16 stimuli remained on screen until the key press wasregistered. The inter-stimulus interval randomly varying between 1 and 3seconds. The task was scored for accuracy (% correct) and reaction time(ms).

For Choice Reaction Time accuracy there was a significant main effect oftreatment [F(3,162=3.406, p=0.021). Comparisons of each dose at eachtime point revealed significant improvements associated with the 100 mgdose at all three time points. There were also significant improvementsfor 200 mg at 1 hr and both 200 mg and 100 mg at 6 hrs (P<0.05 in allcases).

Example 2

Administering American Ginseng served to improve Immediate Word Recallin the following situation.

Word Presentation: Ten common English words appropriate for the agerange of participants were drawn fromhttp://www.math.vorku.ca/SCS/Online/paivio/. Words were matched forlinguistic familiarity, concreteness and frequency and presented insequence on the monitor for the participant to remember at thecommencement of the battery. Stimulus duration was 1 s, as was theinter-stimulus interval.

Immediate word recall. The participant was allowed 60 s to write down asmany of the retained words as possible. The task was scored for numberof correct answers, errors and intrusions and the resulting score wasconverted into a percentage.

There was a significant Treatment×Time interaction [F(6,174=2.399,p=0.03)]. Comparisons of each dose at each time point revealedsignificant improvements associated with the 200 mg dose at all threetime points. The were also significant improvements for 400 mg at 1 hrand 100 mg at 6 hr only (p<0.05 in all cases). Results are shown in FIG.2.

Example 3

Administering American Ginseng served to improve Numeric Working Memoryspeed in the following situation.

Numeric Working Memory: A series of five digits was presented on thecomputer screen sequentially for the participants to hold in theirmemory. This is followed by a series of 30 probe digits. Theparticipants decided whether or not the digit was from the originalseries and indicated their choice by pressing corresponding keyslabelled ‘YES’ and ‘NO’. This was repeated three further times withdifferent stimuli sets. Reaction times (ms) and accuracy (% correct)were measured.

There was a significant main effect of Treatment for Numeric WorkingMemory speed. Comparisons of each dose at each time point revealedsignificant improvements associated with the 200 mg dose at all threetime points. (p<0.05 in all cases).

Example 4

Administering American Ginseng improved Alphabetic Working Memory in thefollowing situation.

Alphabetic Working Memory: This was similar to the numeric workingmemory but using letters. A series of 5 letters appeared on the screenfor participant to remember. After 4 seconds the letters disappeared andwere followed by a series of 30 probe letters. Participants wereinstructed to indicate whether the target letter had appeared in theoriginal list of five letters by pressing corresponding ‘YES’ or ‘NO’key as quickly as possible. The measures were the percentage of thecorrectly identified stimuli and the average reaction time (ms).

There was a trend for a main effect of Treatment for Alphabetic WorkingMemory [F(3,60)=2.7, p=0.063]. This trend merited further explorationand comparisons of each dose at each time point revealed significantimprovements associated with the 100 mg and 400 mg doses at all threetime points (p<0.05 in all cases).

Example 5

Administering American Ginseng served to improve spatial span in thefollowing situation.

Corsi Blocks: The Corsi Block-Tapping Task (initially developed byCorsi, 1972) is a span task and a visuospatial analogue to the digitspan of verbal short-term memory (Lezak, 1995). A computerized versionof the Corsi blocks task was employed in the study. A series of squaresappeared on the screen. A number of these illuminated sequentially inquasi-random order. The volunteer then attempted to repeat the patternby clicking the boxes in the same order with the mouse and cursor. Thedifficulty increases from 4 blocks upwards. The task gives a measure ofspatial span as well as speed of responding.

There was a significant main effects of Treatment on mean Corsi blockscore [F(3,114)=2.925, p=0.041]. Comparisons of each dose at each timepoint revealed significant improvements associated with the all doses atall time points. (p<0.05 in all cases).

Example 6

Administering American Ginseng served to improve calmness in thefollowing situation.

Depression Anxiety and Stress Scale (DASS; Lovibond & Lovibond, 1995):The shortened 21-item version of the DASS was used to assess threenegative affective states of depression, anxiety and stress onseven-item scales. The Depression subscale (DASS-D) measures symptomsrelating to dysphoric mood (e.g. sadness), for example “I couldn't seemto experience any positive feeling at all.” The Anxiety subscale(DASS-A) assesses symptoms associated with physiological hyperarousalsuch as autonomic arousal, for example “I felt I was close to panic.”The Stress subscale (DASS-S) assesses symptoms associated with nervousarousal, for example “I tended to over-react to situations.”Participants were required to indicate on a 4-point scale whether eachstatement applied to them not at all, to some degree, a considerabledegree, or most of the time. Scores were calculated by summing thescores of the appropriate items. Good internal consistency and validityfor the DASS have been found with samples of clinical patients andnon-clinical volunteers (Anthony et al., 1998).

State-Trait Anxiety Inventory (STAI) The State-Trait Anxiety Inventory(STAI) (Speilberger et al, 1969) comprises of two scales. The ‘State’(STAI-S) subscale is a widely used instrument for measuring fluctuatinglevels of anxiety. The subscale contains 20 statements (e.g. ‘I amcalm’). Participants rate how much they feel like each statement at thetime of making the response by marking a 4-point scale ranging from “notat all” to “very much so.” The “Trait’ (STAI-T) subscale comprises 20different statements (e.g. “Some unimportant thought runs through mymind and bothers me”). Participants are asked to indicate how theygenerally feel on a scale ranging from “almost never” to “almostalways.” Scores on both sections of the STAI range from 20 to 80, withhigher scores indicating more anxiety.

Symptom checklist: The symptom checklist consisted of 28physiological/psychological problems people might have (e.g. I feeldizzy, I have a dry mouth, I feel anxious more than usual). Participantsindicated how much the problem had bothered them in the last 7 daysincluding today using a 5-point scale from “not at all” to “very muchso.”

There was a single significant effect on mood measures. TheTreatment×Time interaction on self-rated calmness was significant[F6,150=2.345, p=0.034]. Comparisons of each dose at each time pointrevealed significant improvements associated with the 100 mg dose at 3 hand 6 h only (p<0.05 in both cases).

One skilled in the art will appreciate that the present invention can bepracticed by other than the embodiments disclosed herein, which arepresented for purposes of illustration, and not of limitation.

1. A method of enhancing cognitive performance by administering anamount of American Ginseng effective to treat a subject.
 2. The methodof claim 1 wherein the amount American Ginseng administered comprisesbetween about 5 mg and about 50 mg total ginsenosides.
 3. The method ofclaim 1 wherein the cognitive performance is Attention, measured usingthe Choice Reaction Time test.
 4. The method of claim 3 wherein theamount of American Ginseng administered comprises about 11.65 mg totalginsenosides.
 5. The method of claim 4 wherein the amount of AmericanGinseng is administered more than about 6 hours before desired results.6. The method of claim 3 wherein the amount of American Ginsengadministered comprises about 23.30 mg total ginsenosides.
 7. The methodof claim 6 wherein the amount of American Ginseng is administered morethan about 1 hour before desired results.
 8. The method of claim 6wherein the amount of American Ginseng is administered more than about 6hours before desired results.
 9. The method of claim 1 wherein thecognitive performance is Working Memory, measured using the ImmediateWord Recall test.
 10. The method of claim 9 wherein the amount ofAmerican Ginseng administered comprises about 23.30 mg totalginsenosides.
 11. The method of claim 9 wherein the amount of AmericanGinseng administered comprises about 46.60 mg total ginsenosides. 12.The method of claim 11 wherein the amount of American Ginseng isadministered more than about 1 hour before desired results.
 13. Themethod of claim 9 wherein the amount of American Ginseng administeredcomprises about 11.65 mg total ginsenosides.
 14. The method of claim 13wherein the amount of American Ginseng is administered more than about 6hours before desired results.
 15. The method of claim 1 wherein thecognitive performance is Working Memory, measured using the NumericWorking Memory test.
 16. The method of claim 15 wherein the amount ofAmerican Ginseng administered comprises about 23.30 mg totalginsenosides.
 17. The method of claim 1 wherein the cognitiveperformance is Working Memory, measured using the Alphabetic WorkingMemory test.
 18. The method of claim 17 wherein the amount of AmericanGinseng administered comprises about 11.65 mg total ginsenosides. 19.The method of claim 17 wherein the amount of American Ginsengadministered comprises about 46.60 mg total ginsenosides.
 20. The methodof claim 1 wherein the cognitive performance is spatial span.
 21. Themethod of claim 9 wherein the amount of American Ginseng administeredcomprises about 11.65 mg total ginsenosides.
 22. The method of claim 9wherein the amount of American Ginseng administered comprises about23.30 mg total ginsenosides.
 23. The method of claim 9 wherein theamount of American Ginseng administered comprises about 46.60 mg totalginsenosides.
 24. The method of claims 1, 2, 3, 9, 15, 17, or 20 whereinthe amount of American Ginseng administered also improves calmness. 25.The method of claim 23 wherein the amount of American Ginsengadministered comprises about 11.65 mg total ginsenosides, and theAmerican Ginseng is administered more than about 3 hour before desiredresults.
 26. The method of claim 23 wherein the amount of AmericanGinseng administered comprises about 11.65 mg total ginsenosides, andthe American Ginseng is administered more than about 6 hour beforedesired results.
 27. The method of claim 1 wherein the American Ginsengcomprises ginsenosides in the proportion of about 3 parts Rg₁, about 22parts Re, about 61 parts Rb₁, about 20 parts Rc, about 3 parts Rb₂, andabout 16 parts Rd.